Predictors of mesh infection and explantation after abdominal wall hernia repair

Accepted Manuscript Predictors of mesh infection and explantation after abdominal wall hernia repair José Bueno Lledó, Ph.D., Antonio Torregrosa Gallud, Ph.D., Angela Sala Hernandez, M.D., Fernando Carbonell Tatay, Ph.D., Providencia García Pastor, M.D., Santiago Bonafé Diana, M.D., José Iserte Hernández, M.D. PII:

S0002-9610(16)30243-4

DOI:

10.1016/j.amjsurg.2016.03.007

Reference:

AJS 11935

To appear in:

The American Journal of Surgery

Received Date: 19 November 2015 Revised Date:

16 March 2016

Accepted Date: 29 March 2016

Please cite this article as: Bueno Lledó J, Torregrosa Gallud A, Sala Hernandez A, Carbonell Tatay F, García Pastor P, Bonafé Diana S, Iserte Hernández J, Predictors of mesh infection and explantation after abdominal wall hernia repair, The American Journal of Surgery (2016), doi: 10.1016/ j.amjsurg.2016.03.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT TITLE PAGE Title: Predictors of mesh infection and explantation after abdominal wall hernia repair.

Description of the type of study: A retrospective study

Authors:

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José Bueno Lledó, Ph.D. Antonio Torregrosa Gallud, Ph.D. Angela Sala Hernandez, M.D. Fernando Carbonell Tatay, Ph.D Providencia García Pastor, M.D.

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Santiago Bonafé Diana, M.D.

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José Iserte Hernández, M.D.

Surgical Unit of Abdominal wall. Department of Digestive Surgery. Politecnic “La Fe” Hospital. University of Valencia, Valencia, Spain

Corresponding author: José Bueno Lledó.

Phone. 651 525 437

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Calle Gabriel Miró 28, puerta 12. 46008 Valencia

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e-mail: [email protected]

Running title: Mesh infection and explantation after hernia repair

ACCEPTED MANUSCRIPT Abstract Background. The main objective was to identify predictive factors associated with prosthesis infection and mesh explantation after abdominal wall hernia repair (AWHR).

Methods. Retrospective review of all patients who underwent AWHR between January 2004 and May 2014 at a tertiary center. Multivariate analysis identified predictors of mesh infection

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and explantation after AWHR.

Results. From 3470 cases of AWHR, we reported 66 cases (1.9%) of mesh infection, and 48 repairs (72.7%) required mesh explantation. Steroid or immunosuppressive drugs use (OR 2.22; CI 1.16-3.95), urgent repair (OR 5.06; CI 2.21-8.60), and postoperative surgical site

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infection (OR 2.9; CI 1.55-4.10) were predictive of mesh infection. Predictors of mesh explantation were type of mesh (OR 3.13; CI 1.71-5.21), onlay position (OR 3.51; CI 1.23-6.12),

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and associated enterotomy in the same procedure (OR 5.17; CI 2.05-7.12).

Conclusions. Immunosuppressive drugs use, urgent repair, and postoperative surgical site infection are predictive of mesh infection. Risk factors of prosthesis explantation are PTFE

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mesh, onlay mesh position and associated enterotomy in the same procedure.

Mini-Abstract

Infection is one of the most devastating complications after the implantation of mesh in abdominal wall hernia repair (AWHR). The main purpose of this retrospective study was to identify the incidence and predictive factors associated with prosthesis infection and mesh

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Keywords

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explantation after AWHR.

Mesh infection, mesh explantation, biofilm, abdominal wall hernia, hernia repair, prosthesis infection.

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ACCEPTED MANUSCRIPT Introduction The use of the prosthesis in the abdominal wall hernia repair (AWHR) has introduced new problems. Although mesh has reduced hernia recurrence rates, it has its own set of complications. So, infection is one of the most devastating complications after the implantation of any mesh (1). The risk of infection in AWHR appears to be higher than other clean cases, but there is a wide

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range reported from 1% to 10% (2) depending on the type of mesh, technique, and patient population. Infection of abdominal wall prostheses can have grave and costly consequences and severe impact on the patient’s life due to prolonged hospitalizations and multiple reinterventions, as well as very elevated social costs (3). So, these are an incentive to explore any and all means that might reduce the incidence of mesh infection.

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Over the years, numerous types of prosthesis have been developed to provide greater strength and lower recurrence rates, and at the same time, the risk of infection and other complications have been decreased (4). Some known risk factors for mesh infection have been reported:

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prolonged operative time or type of mesh are predictive factors in heterogeneous series of groin hernia repairs or AWHR (5-7). On the other hand, postoperative surgical site infections or concomitant intraabdominal procedures have been related to mesh explantation in hernia repair (8). But no previous study has been conducted considering factors relating the mesh infection and explantation following AWHR together.

The main purpose of this retrospective study was to identify the incidence, etiologies, and

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independent predictors associated with prosthesis infection and mesh explantation after AWHR.

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ACCEPTED MANUSCRIPT Material and Methods A retrospective review was performed of all patients who underwent AWHR between January 2004 and May 2014 at a tertiary center. Only patients admitted for hernia repair with prosthesis were considered. Patients with laparoscopic hernia repair were excluded. Prosthetic infection was diagnosed when pathogenic organisms were found in the periprosthetic fluid obtained by surgical drainage or percutaneous puncture using ultrasound. Minor infections

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such as cellulitis that could be treated with antibiotics alone were not included in the mesh infection group. Patients who underwent subsequent mesh-related infection were compared with patients without infection: all factors related to mesh infection were collected by retrospective revision of clinical data.

The treatment of prosthetic infection consisted on antibiotics according to antibiogram,

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percutaneous drainage, or standard wound debridement under general or local anaesthesia. If the infection remained, despite these measures, the prosthesis was removed. Mesh explantation was defined as any surgery where the prosthesis was partially or completely

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removed in a subsequent procedure. Reasons for abdominal reoperation and mesh explantation were documented. Further analysis of patients who required complete or partial mesh removal following the index surgery was compared with patients who did not require it. All patients maintained prophylactic antithrombotic (subcutaneous enoxaparin) and prophylactic dose of antibiotic at the moment of mesh implantation. Patients who needed surgery of mesh explantation received antibiotic therapy according to previous antibiogram. Demographic variables including patient’s age and sex were collected. The following medical

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comorbidities were reported: body mass index, chronic obstructive pulmonary disease, steroid use, immunosuppression, diabetes mellitus, smoking history and American Society of Anaesthesiologist (ASA) score. Types and sizes of mesh were identified using physicianabstracted operative notes and we further classified into onlay, underlay or inlay. Microbiology

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data were collected on all patients. Additional variables of interest included postoperative surgical site infection (SSI), and history of previous surgical debridement. Hernia characteristics collected included emergency repair, number of previous hernia repairs, type of repair, drain

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use, concomitant repair (where another procedure was performed at the same time such as enterotomy and ventral hernia repair), recurrent hernia, and hernia location. In addition, the type of removed mesh and any related intra- or post-operative complications were also noted. Patients were followed up at 1 month, 3 months and 1 year after surgery (and subsequent annual reviews). Long-term readmission or referral to another hospital were checked through the hospital database.

In the statistical analysis, a commercial software program (SPSS version 20.0) was used. Univariate analysis was performed using “t-Student” to explore quantitative variables and "Chi square" (or Fisher test) if they were dichotomous. Univariate variables with significance values p <0.05 were included in a logistic regression analysis, identifying independent predictors of mesh infection and explantation, expressed in terms of "odds ratio" (OR) and confidence interval (CI) of 95%. The significance level was p <0.05.

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ACCEPTED MANUSCRIPT Results Over the 10-year study period (January 2004 and May 2014), 3470 AWHR were performed at our Hospital. At a median of 50.6 months (range 14-85 months) of postoperative follow-up, we reported 66 cases of mesh infection, and 48 repairs (72.7%) required mesh explantation. The overall infection rate in AWHR was 1.9%.

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Mesh infection Characteristics were distributed equally in the subgroups with and without prosthetic infection (Table 1). The average age of the mesh infection group was 55.3 ± 21.6 years, and the population was predominantly female (53.1%). Sixteen patients were diabetic, 50.5% suffered from hypertension and 13.5% had chronic obstructive pulmonary disease. Approximately, 9%

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(307/3404) of repairs were performed in patients with immunosuppressive therapy, mainly hepatic and kidney transplantation; of them, 5.4% (16/307) of patients developed mesh infection. Body mass index (BMI) superior to 30 was observed in 49 cases (74.2%). Almost half

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of patients smoked at the moment or had a history of using tobacco (46.9%).

According to type of hernia repair, we found mesh infection in 6 patients with Lichtenstein repair (9% of repairs with prosthesis infection), 2 patients with Rutkow-Robbins technique (3%), 5 cases in Rives-Stoppa technique (7.5%), 11 patients in component separation technique (16.6%), 15 cases in preperitoneal repair (22.7%), and 27 cases with Chevrel technique (40.9%).

In 22 patients, intestinal resection was planned in a concomitant procedure with the ventral

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hernia repair (partial or complete colectomy in 18 cases, small bowel surgery in 4 cases). In 32 patients, enterotomy was unplanned: 20 cases with intestinal perforation during adhesiolysis of the hernia sac, and 12 urgent cases that needed intestinal resection and prosthetic hernia repair.

On univariate analysis, risk factors associated to mesh infection were: BMI>30 (p<0.002),

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smoking (p<0.001), steroid or immunosuppressive drugs use (p<0.020), urgent repair (p<0.001), operative time in previous repair >180 minutes (p<0.003), onlay mesh position

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(p<0.017), very large prosthesis size (p<0.001), concomitant enterotomy with hernia repair (p<0.002) and postoperative surgical wound infection (p<0.001). On multivariate analysis, immunosuppressive drugs use (OR 2.22; CI 1.16-3.95, p=0.016), urgent repair (OR 5.06; CI 2.21-8.60, p=0.001), and development of a postoperative surgical site infection (OR 2.9; CI 1.55-4.10, p=0.002) were predictive of mesh infection. There was no difference in the infection rate among repairs of primary and recurrent hernias, prosthesis type, operative time, type of repair, drain use, hernia defect location, obesity or other comorbidities. The types of contaminating organisms identified on the infected mesh are shown in Table 2. Overall, gram-positive organisms were found in 78.6%, and gram-negative organisms in 21.4%. Eight of the 66 patients had polymicrobial infections. Staphylococcus aureus and Methicillinresistant Staphylococcus aureus (MRSA) were the most common organisms, which were found in 61.5%.

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ACCEPTED MANUSCRIPT Mesh explantation From 66 patients with mesh infection, we identified 48 (72.7%) that required subsequent mesh explantation. The interval between mesh infection and re-operation to mesh removal was 7.3 months (range 1–16 months). The most common reasons for mesh explantation on univariate analysis were BMI>30 (p=0.002), steroid and immunosuppressive drugs use (p=0.002), hernia defect location (p=0.047), operative time in previous repair >180 minutes (p=0.019), urgent

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repair (p=0.001), PTFE mesh (p=0.002), onlay position (p=0.001), and concomitant enterotomy (p=0.002) (Table 3).

On multivariate analysis, the independent predictors of mesh explantation due to infection were type of mesh (OR 3.13; CI 1.71-5.21, p=0.001), onlay position (OR 3.51; CI 1.23-6.12, p=0.003), and associated enterotomy in the surgical procedure (OR 5.17; CI 2.05-7.12,

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p=0.001). So, adjusting for covariates, AWHR with ePTFE placed during an open repair were associated with a 3-fold increase in the hazard of mesh explantation compared with other variables. Patients undergoing a concomitant enterotomy with prosthetic repair were 5 times

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more likely to undergo subsequent mesh explantation, in multivariate analysis. There was no association among comorbidities, prosthesis size or postoperative surgical wound infection and

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subsequent explantation.

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ACCEPTED MANUSCRIPT Discussion Infection of a mesh results in increased patient morbidity due to secondary operations, impaired wound healing, functional loss of the abdominal wall, and significantly extended hospital stay (9). With the high use of synthetic materials for hernia repair, the number of patients that will suffer such infections is likely to increase. It is because of this great morbidity that everything must be done to prevent infection in these patients. Therefore, the study of risk factors in the

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mesh infection and explantation after AWHR is essential to try to minimize its impact. In our cohort of patients followed for a median of 50.6 months, the overall mesh-infection rate was 1.9%, and of them, 72.7% underwent subsequent abdominal reoperation and mesh explantation following AWHR. The literature reports a very wide range of infection rates for AWHR from 0.5% to 30% (3,10), and mesh explantation in cases of prosthetic infection

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following AWHR is common (11). The timeframe from hernia repair to mesh infection in our serie was 10.3 months (range 1-29 months) and the interval between mesh infection and reoperation to mesh removal was a median of 7.3 months (range 1–16 months). This is in

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agreement with other authors, who have described the onset of infection of the mesh with a striking delay of up to 39 months after implantation, due to continuing presence of bacteria from the introduction during surgery onward (12,13). In most cases, the bacteria are protected from the immune response of the host and antibiotics by a biofilm (14).

This biological response to surgically implanted prosthetic materials has been extensively studied (15). The initial reaction, characterized by acute inflammatory cell infiltration, is gradually replaced by fibroblasts (which infiltrate through the interstices of porous meshes) and a variable

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number of giant cells. The most important of these reasons relates to the fibroblastic response of the organism to the polymer of the implanted mesh, which results in the development of a thick fibrous capsule surrounding the mesh. Consequently, when an infection is established, this capsule restricts the penetration of antimicrobial agents into the infected mesh (16). Long-lasting infections on surgical meshes are considered as consisting of multiple different

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bacterial strains (6,17). The majority of our infections (78.6%) involved gram-positive organisms, and Staphylococcus aureus and MRSA were the most common organism, which were found in

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61.5%. This fact can suggest that skin/deeper SSI was the root cause of some of the mesh infections. This is in agreement with other reported series in the literature that showed these organisms as the predominant pathogen in incisional hernia mesh infections (16,17). According to these findings, any patient who presents a mesh infection after an AWHR should be placed on an antibiotic with activity against MRSA and gram-positives (18). On the other hand, our dataset showed that 27% of infections were caused by gram-negative organisms (mainly Enterobacteriaceae) and 24% were polymicrobial. These data are higher than reported previously (9), possibly because of the frequent association of abdominal surgery with enterotomy and AWHR in our group: of 54 patients operated jointly, 6 had mesh infection (11.2%). In our analysis, treatment with corticosteroids or immunocompromised agents represents a predictor of mesh infection, but not explantation. This factor is important due to significant

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ACCEPTED MANUSCRIPT incidence of incisional hernia repairs after kidney, pancreatic or hepatic transplantation (4). Hernias following abdominal organ transplantation are of particular concern as patients are placed on immunosuppressive medications postoperatively, which may increase the risk of incisional hernia formation due to an associated impairment in the wound healing process. In fact, to produce an overall reduction in the immune response, this medication also facilitates the development of bacterial biofilm, an essential factor in resistance of microorganisms to

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antibacterial mechanisms; bacteria secrete a sort of polymer gel within which they become encased and which protects them from antibacterial agents and is a source of persistent or chronic infection (14).

Our findings show that urgent repair and postoperative SSI predispose mesh infection, but not explantation. Other studies identified that SSI was associated with mesh infection and removal;

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however, postoperative outcomes to predict mesh explantation are not clinically useful (7,19). A distinction must be made between superficial wound infection and deep graft infection. In case of superficial infection, it occurs in the early postoperative period, and do not seem to be

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influenced by the use of mesh. Combination of antibiotics (for cellulitis) and drainage (for subcutaneous collection) may result effective, and in these circumstances removal of the prosthesis may not be necessary for complete healing (6).

Therefore, we show that mesh explantation after prosthesis infection is significantly more likely after repairs involving planned concomitant surgery on the gastrointestinal tract, than those using ePTFE-containing mesh products or those with onlay repairs. Clinical studies that have been published on infection rates of abdominal wall implants, demonstrate that the incidence of

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infection depends heavily on the type of mesh and surgical technique applied (6,7). According to our study, the type of prosthesis does not affect the appearance of prosthetic infection but influences the need of explantation. So, ePTFE and dual meshes need complete removal to solve the chronic infection, while 36% of Polypropylene (PPL) meshes does not require reoperation to remove them.

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PPL meshes show infection rates ranging from 2.0–4.2% (20,21). In contrast, ePTFE shows more wide-ranging infection rates ranging from 0.5% to 9.2% when an open surgical approach

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is used (22), and only up to 3% when a laparoscopic approach is used (23,24). In our experience, all meshes have the potential to become infected. Although there is still not enough data in the literature to suggest that one material is far superior to another, it has reported that conservative treatment (drainage and antimicrobial agents only) allowed mesh preservation in most of polyester or PPL meshes, but not in infected ePTFE ones (2,5). The microporous surface of the ePTFE allows bacterial contamination but leucocytes cannot invade the 10 mm pores (25). This fact may explain the pathophysiology of chronic infections and later presentations that can be seen with this mesh. An infected ePTFE patch should therefore be removed early and the necessarily developing hernia recurrence should be closed later (13). Like other series (5,6,26), our data showed that, except in one case, all contaminated ePTFE patches had to be removed. So, AWHR with ePTFE placed during an open repair were

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ACCEPTED MANUSCRIPT associated with a 3-fold increase in the hazard of mesh explantation compared with other variables. Onlay mesh position is a predictive factor for mesh explantation. Some authors have speculated that a reduction in exposure to skin flora and the thickness of wound coverage by muscle and fatty tissue protects against infection (27). This is supported by the low infection rate after hernia repair by the preperitoneal technique or laparoscopic approach, from 0% to 3% (28). In our

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study, laparoscopy was an exclusion criteria because we have no experience in this procedure. We have made fewer than 30 cases during the study period and we believe that the results from this analysis would not be significant.

Several main approaches to the prevention of mesh infection have been used; however, no definitive recommendation can be made in favour of the use of prophylactic antibiotics (systemic

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or topical) in hernia repair (29). As our study, clinical routine still uses a single prophylactic dose of systemic antibiotics at the moment of implantation to prevent biomaterial centred infections in the recovering patient. Unfortunately, there is little direct clinical evidence to base

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recommendations when implantable mesh is used (30) .

Mesh coating has been a subject of research for a long time. However, human studies on the efficacy of antibiotic-coated mesh in the prevention of mesh infection would be difficult to carry out, as a large number of participants will be required to demonstrate a statistically significant result (31). Although our group did not use these materials, the wound can be rinsed with an antibiotic containing solution, starting immediately after the dissection of the hernia sac. In randomised trials who underwent inguinal hernia repair, there were no deep infections following

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the application of a single dose of cefamandole directly to the wound (32) or gentamicin placed on the mesh in vivo (33) or in vitro (34). But at the present time, these measures are best reserved for patients at high risk of infection, such as diabetic and obese patients. A more recent study, showed that diclofenac and ibuprofen in the concentration obtained in vitro in the serum limit the formation of biofilm by S. aureus and E. coli (35): the effect of isolates incubation

surface.

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in the medium with NSAIDs was the decrease of the number of bacteria adjacent to the PPL

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Finally, more important than the choice of antibacterial is the observance of strict asepsis during mesh preparation and implantation (30). In recent years, we have applied preventive measures such as careful and meticulous surgical technique, avoiding bruises and dead spaces with suction drains, manipulating the prosthesis as little as possible, avoiding direct contact between prosthesis and the skin, changing gloves when inserting the prosthesis, preventing foreign bodies, and monitoring the state of the wound edges. It remains clear that bacterial contamination of the prosthesis happens during its initial implantation (7).

In conclusion, infection has become one of the most prevalent and challenging complications in AWHR. Steroid or immunosuppressive drugs use, urgent repair, and development of a postoperative surgical site infection are predictive of mesh infection. Risk factors of explantation are PTFE mesh, onlay mesh position, and associated enterotomy in the same procedure.

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ACCEPTED MANUSCRIPT References 1. Krpata DM, Blatnik JA, Novitsky YW, et al. Evaluation of high-risk comorbid patients undergoing open ventral hernia repair with synthetic mesh. Surgery 2013;153:120–125. 2. Brown RH, Subramanian A, Hwang CS, et al. Comparison of infectious complications with synthetic mesh in ventral hernia repair. Am J Surg 2013; 205:182–187. 3. Falagas ME, Kasiakou SK. Mesh-related infections after hernia repair surgery. Clin Microbiol

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Infect 2005; 11: 3–8. 4. Guillion JF, Palot JP. Abdominal wall incisional hernias: Infected prosthesis: treatment and prevention J Visc Surg 2012: 149;20-31.

5. Bueno J, Sosa Y, Gomez I Gavara I, et al. Infeccion de la protesis en la reparacion herniaria. Nuestra experiencia en 5 años. Cir Esp 2009; 85:158-163.

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6. Petersen S, Henke G, Freitag M, et al. Deep Prosthesis Infection in Incisional Hernia Repair: Predictive Factors and Clinical Outcome. Eur J Surg 2001; 167: 453–457.

7. Mann D, Prout J,Havranek E, et al. Late-Onset Deep Prosthetic Infection following Mesh

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Repair of Inguinal Hernia. Am J Surg 1998:176;12-14.

8. Hawn M, Gray S, Snyder C, et al. Predictors of mesh explantation after incisional hernia repair. Am J Surg 2011; 202: 28–33.

9. Egelsman AF, Van der Mei HC, Ploeg RJ, et al. The phenomenon of infection with abdominal wall reconstruction. Biomaterials 2007;28:2314-2327.

10. Grant AM, EU Hernia Trialists Collaboration. Open mesh versus non-mesh repair of groin hernia: meta-analysis of randomised trials based on individual patient data. Hernia

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2002;6(3):130-6.

11. Trunzo JA, Ponsky JL, Jin J, et al. A novel approach for salvaging infected prosthetic mesh after ventral hernia repair. Hernia 2009;13:545-549. 12. Coda A, Botto-Micca F, Botto-Micca F. Reoperations for chronic infections following prosthetic hernia repair. Hernia 1998;2: 163–167

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13. Leber GE, Garb JL, Alexander AI, et al. Long-term complications associated with prosthetic repair of incisional hernias. Arch Surg 1998; 133: 378–382.

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14. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science 1999;284:1318-1322. 15. Chung L, Tse GH, O’Dwyer PJ. Outcome of patients with chronic mesh infection following abdominal wall hernia repair. Hernia 2014; 18:701–704 16. Buret A, Ward KH, Olson ME, et al. An in vivo model to study the pathobiology of infectious biofilms on biomaterial surfaces. J Biomed Mater Res 1991; 25: 865–874. 17. Rios A, Rodriguez JM, Munitiz V, et al. Antibiotic prophylaxis in incisional hernia repair using a proshtesis. Hernia 2001;5:148–152. 18. Ousley J, Baucom RB, Stewart MK, et al. Previous Methicillin-Resistant Staphylococcus aureus Infection Independent of Body Site Increases Odds of Surgical Site Infection after Ventral Hernia Repair. J Am Coll Surg. 2015;221:470-477.

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ACCEPTED MANUSCRIPT 19. Liang MK, Li LT, Nguyen MT, et al. Abdominal reoperation and mesh explantation following open ventral hernia repair with mesh. Am J Surg. 2014;208:670-676. 20. Dunne JR, Malone DL, Tracy JK, et al. Abdominal wall hernias: risk factors for infection and resource utilization. J Surg Res 2003;111:78-84. 21. Neumayer L, Giobbie-Hurder A, Jonasson O, et al. Open mesh versus laparoscopic mesh repair of inguinal hernia. N Engl J Med 2004;350:1819–1827.

intraperitoneal placement of ePTFE. Am J Surg 1999;177:291–293.

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22. Gonzalez AU, De la Portilla F, Albarran GC. Large incisional hernia repair using

23. LeBlanc KA. Laparoscopic incisional and ventral hernia repair: Complications—how to avoid and handle. Hernia 2004;8:323–331.

24. Berger D, Bientzle M, Muller A. Postoperative complications after laparoscopic incisional

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hernia repair. Surg Endosc 2002;16:1720–1723.

25. Amid PK. Classification of biomaterials and their related complications in abdominal wall hernia surgery. Hernia 1997;1:15–21.

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26. Pennington DG, Lam T. Gore-Tex patch repair of the anterior rectus sheath in free rectus abdominis muscle and myocutaneous flaps. Plast Reconstr Surg 1996; 97: 1436–1440. 27. Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med 2004;350:1422-1429.

28. Topart P, Ferrand L, Vandenbroucke F, et al. Laparoscopic ventral hernia repair with the Goretex Dualmesh: long-term results and review of the literature. Hernia 2005;9:348–532. 29. Mazaki T, Mado K, Masuda H, et al. A randomized trial of antibiotic prophylaxis for the

2014;207:476-484.

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prevention of surgical site infection after open mesh-plug hernia repair. Am J Surg.

30. Deysine M. Infection control in a hernia clinic: 24 year results of aseptic and antiseptic measure implementation in 4,620 "clean cases". Hernia. 2006;10:25-29. 31. Majumder A, Novitsky YW. Antibiotic Coating of Hernia Meshes: The Next Step Toward

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Preventing Mesh Infection. Surg Technol Int. 2015;7:27-14. 32. Lazorthes F, Chiotasso P, Massip P, et al. Local antibiotic prophylaxis in inguinal hernia

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repair. Surg Gynecol Obstet. 1992; 175:569-570 33. Musella M, Guido A, Musella S. Collagen tampons as aminoglycoside carriers to reduce postoperative infection rate in prosthetic repair of groin hernias. Eur J Surg 2001;167:130–132. 34. Wiegering A, Sinha B, Spor L, et al. Gentamicin for prevention of intraoperative mesh contamination: demonstration of high bactericide effect (in vitro) and low systemic bioavailability (in vivo). Hernia. 2014;18:691-700. 35. Reśliński A, Dąbrowiecki S, Głowacka K. The impact of diclofenac and ibuprofen on biofilm formation on the surface of polypropylene mesh. Hernia. 2015;19:179-185.

ACCEPTED MANUSCRIPT

NO MESH INFECTION GROUP (%) N= 3404

MESH INFECTION GROUP (%) N= 66

Univa riate P

MULTIVARIATE OR (IC95%)

Multiv ariate P

Age (mean±SD) Gender Male Female BMI >30 ≤30 Smoking yes no Diabetes yes no Steroid or immunosuppressive drugs use yes no ASA class I-II III-IV Previous abdominal wall hernia repair yes no Hernia defect location (EHS class.) Groin hernia Midline hernia /umbilical hernia (M1,M2,M3,M4,M5) Lateral hernia (L1,L2,L3,L4) Case status urgent elective Type of repair Lichtenstein Rutkow-Robbins Rives-Stoppa Preperitoneal technique Component separation Chevrel technique Operative time in previous repair < 90 min 91 - 179 min >180 min Mesh position Overlay Underlay (preperitoneal/retromuscular) Intraperitoneal Type of Prosthesis PPL PTFE/ dualmesh PVDF Polyester Biologic Prosthesis size Standard (6x11 cms; 7x15 cms) Large (15x15 cms: 20x15 cms) Very large (20x30cms; 30x30cms or more) Enterotomy (concomitant procedure) Planned (intestinal resection and hernia repair) Unplanned no Drain use yes no (Postoperative) surgical wound infection yes no

53.6 ± 25.5

55.3 ± 21.6

0.116

1.21 (0.91-1.49)

0.121

1528 (44.8) 1976 (55.2)

31 (46.9) 35 (53.1)

0.241

2.14 (0.97-4.69)

0.072

1290 (37.8) 2114 (62.2)

49 (74,2) 17 (25,8)

0.002

1.56 (0.68-2.75)

0.093

851 (25) 2553 (75)

31 (46.9) 35 (53.1)

0.001

1.06 (0.38-2.67)

0.930

667 (19.6) 1737 (80.4)

16 (24.2) 50 (75.8)

0.089

1.82 (0.96-3.46)

0.067

291 (8.5) 3113 (91.5)

16 (24.2) 50 (75.8)

0.020

2.22 (1.16-3.95)

0.016

47 (71.2) 19 (28.8)

0.420

0.55 (0.19-1.57)

0.254

786 (23.1) 2218 (76.9)

17 (25.7) 49 (74.3)

0.272

1.06 (0.42-2.45)

0.098

1801 (52.9) 1358 (39.9) 245 (7.2)

8 (12.1) 54 (81.8) 4 (6.1)

0.060

1.12 (0.74-2.33)

0.059

177 (5.1) 3227 (94.9)

9 (13.6) 57 (86.4)

0.001

5.06 (2.21-8.6)

0.001

1399 (41) 502 (14.7) 258 (7.5) 295 (8.6) 298 (8.7) 652 (19.2)

6 (9) 2 (3) 5 (7.5) 15 (22.7) 11 (16.6) 27 (40.9)

0.234

1.66 (0.32-2.89)

0.088

1913 (56.1) 1036 (30.4) 455 (13.5)

10 (15.1) 22 (33.3) 34 (51.6)

0.003

2.11 (0.89-4.32)

0.056

2025 (59.4) 1335 (39.2) 44 (1.4)

55 (83.4) 11 (16.6) 0

0.017

2.01 (0.55-3.89)

0.062

2408 (70.7) 483 (14.1) 319 (9.3) 169 (4.9) 25 (0.8)

42 (63.6) 18 (27.2) 3 (4.5) 1 (1.5) 2 (3)

0.231

0.90 (0.31-1.99)

0.122

2175 (63.8) 568 (16.6) 661 (19.6)

14 (21.2) 23 (34.8) 29 (44.0)

0.001

1.23 (0.55-2.35)

0.099

20 (0.6) 28 (0.7) 3356 (98.6)

2 (3) 4 (6.1) 60 (90.9)

0.002

1.41 (0.45-3.20)

0.058

1505 (44.2) 1899 (55.8)

25 (37.8) 41 (62.2)

0.342

0.69 (0.23-1.43)

0.721

349 (10.2) 3055 (89.8)

26 (39.3) 40 (60.7)

0.001

2.9 (1.55-4.10)

0.002

TE D

EP

AC C

SC

2561 (75.2) 843 (24.8)

RI PT

VARIABLES

M AN U

Table 1. Predictors of mesh infection. Univariate and multivariate analysis.

SD: standard deviation; BMI: body mass index; EHS class.: European Hernia Society classification.

ACCEPTED MANUSCRIPT Table 2. Contaminating organisms identified on the infected mesh. Microbiology

Number of patients (%) 29 (43.3)

MRSA

12 (18.2)

STAPHYLOCOCCUS EPIDERMIDIS

10 (15.1)

RI PT

STAPHYLOCOCCUS AUREUS

E. COLI

6 (9.1)

ANAEROBIC / ENTEROCOCCUS

9 (13.6)

PSEUDOMONA

4 (6)

PROTEUS

SC

4 (6)

KLEIBSELLIA

M AN U

2 (3)

AC C

EP

TE D

MRSA: Methicillin-resistant Staphylococcus aureus

ACCEPTED MANUSCRIPT Table 3. Predictors of mesh explantation. Univariate and multivariate analysis. Univa riate P

MULTIVARIATE OR (IC 95%)

Multiv ariate P

0.135

0.51 (0.11-1.03)

0.876

20 (41.6) 28 (58.4)

7 (38.8) 11 (61.2)

0.252

2.01 (0.77-3.61)

0.092

40 (83.3) 8 (16.7)

9 (50) 9 (50)

0.002

1.2 (0.28-2.76)

0.343

23 (48) 25 (52)

8 (44.4) 10 (55.6)

0.123

1.11 (0.38-2.31)

0.076

11 (22.9) 37 (72.1)

5 (27.7) 13 (72.8)

0.091

1.48 (0.76-3.21)

0.322

15 (31.2) 33 (68.8)

1 (5.5) 17 (94.5)

0.022

2.22 (0.36-4.91)

0.066

10.2±7.9

0.320

0.55 (0.19-1.57)

0.688

5 (27.7) 11 (61.1)

0.061

1.11 (0.32-2.11)

0.087

2 (4.2) 44 (91.6) 2 (4.2)

6 (33.3) 10 (55.6) 2 (11)

0.047

1.12 (0.74-2.33)

0.434

30 (62.5) 16 (33.3) 2 (4.2)

11 (61.1) 6 (33.3) 1 (5.5)

0.123

1.96 (0.88-3.32)

0.909

5 (10.4) 12 (25) 31 (64.5)

5 (27.7) 10 (55.6) 3 (16.6)

0.019

2.01 (0.55-3.89)

0.104

8 (16.6) 40 (83.4)

1 (5.5) 17 (94.5)

0.001

0.55 (0.23-1.1)

0.072

27 (56.2) 17 (35.4) 2 (4.2) 0 2 (4.2)

15 (83.3) 1 (5.5) 1 (5.5) 1 (5.5) 0

0.004

3.13 (1.71-5.21)

0.001

44 (91.6) 4 (8.4) 0

11 (61.1) 7 (38.9) 0

0.001

3.51 (1.23-6.12)

0.003

4 (8.4) 19 (39.5) 25 (52.1)

10 (55.6) 4 (22.3) 4 (22.3)

0.061

1.9 (0.55-3.33)

0.089

3 (6.2) 3 (6.2) 42 (87.5)

0 0 18 (100)

0.001

5.32 (2.1-7.43)

0.001

21 (43.7) 27 (56.3)

5 (27.7) 13 (72.3)

0.023

0.09 (0.12-1.95)

0.080

40 (83.3) 8 (16.7)

14 (77.7) 4 (22.3)

0.111

0.65 (0.23-1.12)

0.434

11.1±8.3 3 (6.2) 43 (89.5)

RI PT

NO MESH EXPLANTA TION N= 18 53.1± 19.4

AC C

EP

TE D

M AN U

Age (mean ±SD) Gender Male Female BMI >30 ≤30 Smoking yes No Diabetes yes No Steroid or immunosuppressive drugs use yes no Average time of mesh infection in months since the previous mesh implantation (SD) Previous abdominal wall hernia repair yes no Hernia defect location (EHS class.) Groin hernia Midline hernia/ umbilical hernia (M1,M2,M3,M4,M5) Lateral hernia (L1,L2,L3,L4) Symptoms Wound infection Chronic Sinus Mesh extrusion Operative time in previous repair < 90 min 91 - 179 min >180 min Case status Urgent Elective Type of mesh PPL PTFE/Dualmesh PVDF Polyester Biologic Mesh position in hernia repair Onlay Sublay Intraperitoneal Prosthesis size Standard (6x11 cms; 7x15 cms) Large (15x15 cms: 20x15 cms) Very large (20x30 cms; 30x30 cms or more) Enterotomy (concomitant procedure) Planned (intestinal resection and hernia repair) Unplanned no (Postoperative) surgical wound infection yes no Drain use Yes no

MESH EXPLANTA TION N=48 56.9± 22.8

SC

VARIABLES

SD: standard deviation; BMI: body mass index; EHS class.: European Hernia Society classification